Document Detail


Identification of a novel haplotype of the human catechol-O-methyltransferase gene.
MedLine Citation:
PMID:  19077667     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human catechol-O-methyltransferase (COMT; EC 2.1.1.6) catalyzes the transfer of the methyl group to a variety of endogenous and exogenous catechol substrates using S-adenosyl-L-methionine as the methyl donor. This enzymatic O-methylation plays an important role in the inactivation of biologically active and toxic catechols. A number of studies in recent years have sought to characterize the polymorphism of human COMTs and also to determine the catalytic activity of polymorphic enzymes. We report here the identification of a new haplotype of the human COMT gene with triplet point mutations, which encodes the D51G/S60F/K162R mutant of the soluble COMT and the D101G/S110F/K212R mutant of the membrane-bound COMT. Kinetic analysis showed that these new COMT variants had essentially the same kinetic characteristics and catalytic activity as the wild-type COMTs for the O-methylation of 2-hydroxyestradiol and 4-hydroxyestradiol in vitro, but they have a significantly reduced thermostability at 37 degrees C.
Authors:
Hyoung-Woo Bai; Bao Ting Zhu
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  19     ISSN:  1744-6872     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-03-03     Revised Date:  2013-04-22    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  87-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, KS 66160, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Catechol O-Methyltransferase / genetics*,  metabolism
Cloning, Molecular
DNA Primers / genetics
Enzyme Stability
Haplotypes
Humans
Kinetics
Pharmacogenetics
Point Mutation
Recombinant Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
CA 97109/CA/NCI NIH HHS; ES 15242/ES/NIEHS NIH HHS; R01 CA097109/CA/NCI NIH HHS; R01 ES015242/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Recombinant Proteins; EC 2.1.1.6/Catechol O-Methyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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